Non-interventional observational study broadens positive benefit-risk assessment of an immunomodulating herbal remedy in the common cold.

Background: The unique extract of a mixture of Baptisiae tinctoriae radix, Echinaceae pallidae/purpureae radix and Thujae occidentalis herba alleviates the typical symptoms of the common cold and shortens the duration of the disease. Purpose: The risk-benefit ratio of a concentrated formulation of this herbal extract was investigated under everyday conditions. Study design: Pharmacy-based, non-interventional, multicenter, open, uncontrolled study registered at DRKS00011068. Methods: For 10 days, patients completed a diary questionnaire rating the severity of each common cold symptom on a 10-point scale. For evaluation, symptoms were combined into the scores "overall severity", "rhinitis", "bronchitis" and "general symptoms". Cox models were used to evaluate the influence of covariates on the time of stable improvement. Results: In total 955 patients (12 to 90 years) were analyzed; 85% assessed the efficacy as good or very good. Response (improvement of the overall severity by at least 50%) was reached at median day 5 (95% CImedian 5-5). General symptoms abated faster than the other complaints. The percentage of predominantly moderate or severe symptoms to predominantly mild or absent symptoms reversed on day 3.9 (interpolation). Results of adolescents and adults did not differ (p = .6013; HR = 0.918). Concomitant medication did not boost the effect of the herbal remedy. Early start of treatment of the cold accelerated the recovery (p = .0486; HR = 0.814). Thirty-four cases of adverse events were self-recorded in the diaries; none of them were serious. The tolerability was assessed as "good or very good" by 98% of the patients. Conclusion: The benefit-risk assessment of this herbal extract clearly remains positive. This non-interventional study accords with and shows transferability of the results of previous placebo-controlled studies with this extract in a real-life setting.

[Wirksamkeit und Verträglichkeit eines homöopathischen Komplexmittels (Sinusitis Hevert SL) bei akuter, unkomplizierter Rhinosinusitis: Eine multizentrische, randomisierte, doppelblinde, placebokontrollierte Studie an erwachsenen Patienten].

Hintergrund: In der vorliegenden Studie wurden die Wirksamkeit und Verträglichkeit des homöopathischen Arzneimittels Sinusitis Hevert SL an Patienten mit akuter Rhinosinusitis untersucht. Methoden: In einer randomisierten, placebokontrollierten klinischen Studie wurden 314 Patienten mit bis zu 3 Tagen bestehenden Symptomen, leichtem bis moderatem Gesichtsschmerz und einem Major Rhinosinusitis Symptom Score (MRSS) ≥ 8 und ≤ 14 für 15 Tage (Tag 0 erster Arztbesuch plus 14 Tage Behandlung) eingeschlossen und mit Sinusitis Hevert SL oder Placebo behandelt. Den primären Endpunkt bildeten die Responderrate im MRSS (Reduktion ≥ 50%) bei der Abschlussvisite sowie die Rate der Remissionen (komplettes Abklingen aller 5 Hauptsymptome). Sekundäre Zielkriterien bildeten die Einschätzung der Wirksamkeit durch den Prüfer (auf einer 4-Punkte-Skala) und der Sino-Nasal Outcome Test 20 German Adapted Version (SNOT-20 GAV; Selbsterhebung durch die Patienten). Ergebnisse: 314 Patienten wurden in die Studie eingeschlossen. Davon wurden 308 mit der Studienmedikation behandelt: 153 mit Sinusitis Hevert SL und 155 mit Placebo. 265 Patienten schlossen die Studie vollständig und valide ab (Valid Completers). Die MRSSpat-Responderrate aller Patienten war für Sinusitis Hevert SL nicht signifikant besser (85,6% vs. 80,6%; p = 0,243), die Rate der Remissionen war mit 31,4% für Sinusitis Hevert SL und 37,4% für Placebo in beiden Gruppen nicht signifikant unterschiedlich (p = 0,2641). In der sekundären Completer-Analyse zeigte sich eine signifikante Differenz der Responderraten von 92,1% versus 83,5% zugunsten von Sinusitis Hevert SL (p = 0,032). Weiter war die Zeit bis zur Verbesserung der Rhinorrhoe signifikant kürzer (4,0 vs. 6,0 Tage; p = 0,040). Vor allem relevante nasale Symptome des SNOT-20 und die Lebensqualität verbesserten sich unter Behandlung mit Sinusitis Hevert SL signifikant deutlicher. Schlussfolgerungen: Es zeigte sich in dieser Studie bei akuter Rhinosinusitis und hoher Placebo-Ansprechrate keine Überlegenheit für Sinusitis Hevert SL in der Gesamtresponder- und Remissionsrate. Es fand sich ein Nutzen von Sinusitis Hevert SL in der Auswertung der Valid Completers für die Response sowie für spezifische Verbesserungen klinisch relevanter Symptome und die Abheilungsgeschwindigkeit der akuten Rhinosinusitis bei guter Verträglichkeit.

Health-Related Quality of Life During Routine Treatment with the SQ-Standardised Grass Allergy Immunotherapy Tablet: A Non-Interventional Observational Study.

BACKGROUND AND OBJECTIVE: Allergy immunotherapy (AIT) with the SQ(®) grass sublingual immunotherapy (SLIT)-tablet has been shown to be efficacious, well-tolerated and to improve disease-specific health-related quality of life (HRQoL) in controlled clinical trials. The aim of our study was to investigate HRQoL in patients with allergic rhinoconjunctivitis routinely treated with the SLIT-tablet and taking symptomatic medication as needed compared with patients treated only with symptomatic medication. METHODS: In a non-interventional, open-label study, patients treated with the SLIT-tablet were observed for about 12 months compared with patients only symptomatically treated. Patients assessed their HRQoL with the 12-Item Short Form Health Survey (SF-12) and the Rhinitis Quality of Life Questionnaire (RQLQ) in the grass pollen seasons (GPS) at baseline (GPS1, HRQoL1), after GPS1 (HRQoL2) and in the following GPS (GPS2, HRQoL3). Tolerability, compliance, symptoms and medication use were assessed in the SLIT-tablet group by the physician. RESULTS: Overall, data were analysed in 576 patients. Mean differences (±SD) in overall scores for HRQoL3 versus HRQoL1 (186 patients) of SF-12 were +11.4 ± 16.8 (SLIT-tablet) and -3.4 ± 15.7 (symptomatic medication), (p < 0.0001), and of RQLQ -1.31 ± 1.07 and +0.10 ± 0.74 (p < 0.001), and for HRQoL3 versus HRQoL2 (238 patients) of SF-12 -1.6 ± 15.3 and -10.0 ± 14.1 (p = 0.0003), and of RQLQ +0.22 ± 1.29 and +1.24 ± 1.30 (p < 0.0001). Tolerability and adherence for the SLIT-tablet were comparable with data of other non-interventional studies. CONCLUSIONS: Routine treatment with the SQ(®) grass SLIT-tablet resulted in clear improvements in disease-specific and general quality of life, while no improvements were observed in patients treated only symptomatically.

Efficacy of black cohosh (Cimicifuga racemosa) medicines for treatment of menopausal symptoms - comments on major statements of the Cochrane Collaboration report 2012 "black cohosh (Cimicifuga spp.) for menopausal symptoms (review)".

Menopausal symptoms management with high-quality plant extracts from Actaea (Cimicifuga. racemosa rootstock is well-established. Efficacy and safety are supported by research and clinical trials since several decades and backed up by official monographs. However, the recent published Cochrane review on black cohosh neglects major evidence for beneficial effects. The authors' negative conclusions are questionable and call for reply and clarification. Our careful reconsideration of all appropriate placebo-controlled clinical studies reveals a standardized mean difference of 0.385 in favor of black cohosh (p < 0.0001).

Immunologic effect and tolerability of intra-seasonal subcutaneous immunotherapy with an 8-day up-dosing schedule to 10,000 standardized quality-units: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: International guidelines recommend that allergen-specific immunotherapy for pollen-induced rhinoconjunctivitis is initiated preseasonally. However, because subjects often present to physicians with allergy symptoms during the pollen season, "within-season" initiation of specific immunotherapy is of special interest. OBJECTIVE: We evaluated the immunomodulatory effects and tolerability of subcutaneous immunotherapy (SCIT) with Standardized Quality (SQ) 6-grass mix and rye allergen extract, using an 8-day intra-seasonal up-dosing schedule to 10,000 SQ-units (SQ-U). METHODS: In a 9-week, multicenter, randomized, double-blind, placebo-controlled trial, adults (mean age, 34.6 years; 99.3% whites) with grass pollen-induced rhinoconjunctivitis (mean disease duration, 15.1 years) were randomized 3:1 to receive SCIT or placebo. Treatment was initiated during the 2008 pollen season, with an 8-day up-dosing from 100 to 10,000 SQ-U (6 daily injections) followed by 2 maintenance injections of 10,000 SQ-U at intervals of 2 and 4 weeks, respectively. The primary end point examined immunologic effects, assessing the difference in IgE-blocking factor (serum components competing with IgE for allergen binding) between SCIT and placebo at week 9. Secondary/explorative end points included the difference in IgE-blocking factor, specific IgG(4), and specific IgE at various times. Tolerability (adverse events, local and systemic allergic reactions) of the up-dosing schedule was also evaluated. RESULTS: Of the 148 treated subjects 144 (SCIT n = 109; placebo n = 35) were analyzed for the primary parameter. Immunologic response (significantly higher increase in IgE-blocking factor and IgG(4) levels) occurred with SCIT versus placebo at week 9 (IgE-blocking factor, P = 0.0017; IgG(4,)P = 0.0215). Significant differences were observed as early as week 3. AEs were reported in 60.7% of SCIT- and 30.6% of placebo-treated subjects, with no treatment-related serious AEs. Local allergic reactions occurred in 46.4% of SCIT and 8.3% of placebo subjects (χ(2) test, P < 0.0001). No significant difference was observed between groups in the incidence of systemic reactions (7.1% SCIT vs 5.6% placebo; χ(2) test, P = 0.7413). CONCLUSIONS: This trial provides the first description of short (8-day) intra-seasonal up-dosing with SCIT, which induced immunologic effects after only 3 weeks, and was generally well tolerated, although it induced a marked increase in the rate of local reactions compared with placebo. ClinicalTrials.gov identifier NCT00807547; ALK trial ID SHX0562.

Efficacy and safety of a combination herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix for the prophylactic treatment of patients with respiratory tract diseases: a randomised, prospective, double-blind, placebo-controlled phase III trial.

OBJECTIVE: The aim of this ICH-GCP study was to investigate the efficacy and safety of a prophylactic administration of a combination herbal medicinal product (CHMP) in two dosages compared to placebo with respect to the incidence of new occurring infections of the respiratory tract (RTI). Clinical experience of prophylactic treatment of respiratory tract infections with the marketed CHMP containing horseradish root (Armoraciae rusticanae radix) and nasturtium (Tropaeoli majoris herba) has existed for decades. METHODS: The study was performed as a phase III, multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group trial. All groups received two film coated tablets three times a day. Group 1 received the CHMP tablets 3 × 2 per day, group 2 the CHMP tablets 2 × 2 and placebo tablets 2 × 1 per day and group 3 received placebo tablets 3 × 2 per day. Maximum duration of treatment was 84 days. The primary efficacy criterion was the comparison of the incidences of new occurring RTIs between the treatment groups during the prophylactic treatment. In addition the character of occurring infections, number of sick days and severity of infections were compared. Further criteria were subjects' well being, the satisfaction of subjects with the respective treatments and severity and incidence of the observed adverse events (AE) and serious adverse events (SAE) during the study period. TRIAL REGISTRATION: EudraCT No. 2010-023227-26. RESULTS: From 371 subjects screened, a total of 351 subjects of both sexes from 18 to 75 years were randomly allocated to one of the three groups. In order to achieve scientifically and medically impeccable results it was necessary to address acute infections of the respiratory tract occurring during the normal incubation period. Early infections (≤day 7) were excluded from the data set in a sensitivity analysis. In the intention to treat (ITT) population excluding early infections ≤day 7 (n = 344) the infection rates were 13.3% for CHMP 3 × 2 (n = 113), 18.4% for CHMP 2 × 2 (n = 114) and 25.6% for placebo (n = 117). The statistical trend test showed significant results (p = 0.0171). For the per protocol (PP) population - also excluding infections ≤day 7 (n = 334) - infection rates were: CHMP 3 × 2 (n = 110) 12.7%, CHMP 2 × 2 (n = 113) 18.6% and placebo (n = 111) 24.3% (p = 0.0266). Secondary parameters of infections (infection diagnosis, intensity, duration) showed no relevant differences between the treatment groups. The study medication was well tolerated. LIMITATIONS: This was the first clinical ICH-GCP study with the CHMP conducted in this indication and with a sufficient number of subjects. The study population comprised subjects from 18 to 75 years and covered different diagnoses of RTIs. The results show a benefit when using 3 × 2 film tablets of CHMP for prophylaxis of RTIs. However, no data are available on use of the CHMP in this indication in children, adolescents and the elderly (over 75 years). CONCLUSION: This trial demonstrates the efficacy and safety of the combination herbal medicinal product as the treatment of first choice in the prophylactic treatment of episodes of respiratory tract infections. Clinical experience was confirmed in an ICH-GCP study.

Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract.

OBJECTIVE: Black cohosh, a popular herbal treatment for menopausal symptoms, has been implicated in a number of hepatotoxicity case reports. The purpose of this investigation was to analyze data gained from clinical trials on the effect of black cohosh on liver function. METHODS: A meta-analysis of randomized, double-blind, and controlled clinical trials was conducted. These studies primarily evaluated the efficacy and safety of the isopropanolic black cohosh extract (iCR) in perimenopausal and postmenopausal women. Raw data on liver function values of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltranspeptidase were considered in this analysis, if these data at baseline and after 3 to 6 months of treatment were available. Standard methods of descriptive statistics were used in this analysis. RESULTS: Five studies involving a total of 1,117 women were included in the meta-analyses. A total of 1,020 women (test population=517 and reference population=503) completed the studies. Perimenopausal and postmenopausal women (40-60 y) were treated daily with iCR (corresponding to 40-128 mg drug) for 3 to 6 months. The meta-analyses of the standardized mean differences in the "test" versus "reference" showed no significant effects and no differences between double-blind, placebo-controlled and other trials. The overall fixed effect ± SEM was 0.055 ± 0.062 (P=0.37) for aspartate aminotransferase and 0.063 ± 0.062 (P=0.31) for alanine aminotransferase. The nonsignificant effects concerned the overall analyses of all included studies as well as the proportion of placebo-controlled studies. CONCLUSIONS: The results of this meta-analysis of five randomized, double-blind, and controlled clinical trials showed no evidence that iCR has any adverse effect on liver function.

Randomized, placebo-controlled, double-blind trial of Boswellia serrata in maintaining remission of Crohn's disease: good safety profile but lack of efficacy.

BACKGROUND: Complementary therapies are frequently used by patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the efficacy and safety of long-term therapy with a new Boswellia serrata extract (Boswelan, PS0201Bo) in maintaining remission in patients with Crohn's disease (CD). METHODS: In 22 German centers a double-blind, placebo-controlled, randomized, parallel study was performed. In all, 108 outpatients with CD in clinical remission were included. Patients were randomized to Boswelan (3×2 capsules/day; 400 mg each) or placebo for 52 weeks. The primary endpoint was the proportion of patients in whom remission was maintained throughout the 52 weeks. Secondary endpoints were time to relapse, changes of Crohn's Disease Activity Index (CDAI), and IBD Questionnaire (IBDQ) scores. RESULTS: The trial was prematurely terminated due to insufficient discrimination of drug and placebo with regard to the primary efficacy endpoint. A total of 82 patients were randomized to Boswelan (n=42) or placebo (n=40). Sixty-six patients could be analyzed for efficacy. 59.9% of the actively treated patients and 55.3% of the placebo group stayed in remission (P=0.85). The mean time to diagnosis of relapse was 171 days for the active group and 185 days for the placebo group (P=0.69). With respect to CDAI, IBDQ, and laboratory measurements of inflammation, no advantages in favor of active treatment were detected. Regarding safety concerns, no disadvantages of taking the drug compared to placebo were observed. CONCLUSIONS: The trial confirmed good tolerability of a new Boswellia serrata extract, Boswelan, in long-term treatment of CD. However, superiority versus placebo in maintenance therapy of remission could not be demonstrated.

A pollen extract (Cernilton) in patients with inflammatory chronic prostatitis-chronic pelvic pain syndrome: a multicentre, randomised, prospective, double-blind, placebo-controlled phase 3 study.

BACKGROUND: National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. OBJECTIVES: To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. DESIGN, SETTING, AND PARTICIPANTS: We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. INTERVENTION: Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. MEASUREMENTS: The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. RESULTS AND LIMITATIONS: In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. CONCLUSIONS: Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.